Biostatistics Seminar: Guoping Fan

TITLE: Insights into Transcriptome Dynamics in pre-implantation embryos as well as naïve and primed embryonic stem cells

ABSTRACT:

Both human and mouse embryonic stem cells (ESCs) are derived from the inner cell mass of early blastocysts, possessing the potential to differentiate into all cell-types. Moreover, both mouse and human ESCs can be treated with pharmacological compounds including inhibitors targeting GSK3β of the Wnt pathway and MAPK1/2 of the ERK signaling, which cause normal ESCs from “prime” state towards a so-called ground (or “naïve”) state of pluripotency. Transcriptome analysis of these cells confirmed that human and mouse ESCs are in distinctively different states of gene transcription and pluripotency. While transcriptome analysis of mouse naïve ESCs suggests that they seem more similar to inner cell mass, the relationship between various states of pluripotency and early embryos has not been thoroughly studied. In this talk, I will first present our single cell analysis of genetic programs during the progressive development of both human and mouse pre-implantation embryos. Using the method of weighted gene co-expression network analysis (WGCNA), we uncovered sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism in a step-wise fashion. We next examine whether transcriptional network of naïve or primed ESCs resembles that of any pre-implantation stages. Although primed states did not have any similarities with pre-implantation stages, naïve ESCs were similar to morula and blastocyst embryos. Intriguingly, the transcriptional architecture of human naïve ESCs also resembles that of human morula and blastocyst embryos. Furthermore, we identified a number of candidate hub genes that may be key factors in regulating both the naïve state and late pre-implantation development. Taken together, our comprehensive analysis has yielded novel insights into the complex relationship between different types of ESCs and the early developing embryos.